Ex-Vivo Human Clot Analog Fabrication for Mechanical Thrombectomy Device Validation
Montgomery, Nathan Thor
2023
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NTM_Honors_Capstone_Final_Report_-_Nathan_Montgomery.pdf
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Abstract
Introduction: This project aims to contribute towards improved treatment of ischemic stroke. Proper vessel recanalization is essential for ischemic stroke treatment and currently is often done using mechanical thrombectomy devices. To improve recanalization rates and achieve better patient outcomes with new device designs, proper device validation is required. Validation can be more easily, and cost effectively, completed using ex-vivo clot analogs. As such in this project novel ex-vivo clot analogs are fabricated. Various coagulation conditions are explored to form clot analogs that mimic real human thrombi properties so the ex-vivo analogs can be used for thrombectomy device validation. Methods: During project work various blood products and biochemical ingredients were combined in different ratios for different analog fabrication trials. Blood products used included human red blood cells (RBCs) and platelet rich plasma (PRP), and porcine (pig) whole blood. Solutions of CaCl2 were used as clotting initiators and type I collagen and thrombin solutions were used to enhance clot coagulation. Clot analogs were mixed and then allowed to coagulate for 1-2 hours. Coagulation occurred at room temperature or human body temperature of 37 degrees C, and under static or orbital shaking conditions. Fabricated analogs were characterized via dynamic mechanical analysis (DMA) testing and histology imaging. Results: Clot analogs were made in multiple trials differing by ingredients used and coagulation conditions. All trials resulted in solid clot analogs after addition of CaCl2 solution in a 1:10 ratio to blood product volume. Solid clots fully formed after coagulation for 1-2 hours, both at room and human body temperatures, and under static and orbital shaking conditions. For select analog trials DMA testing revealed stiffness properties, and histology imaging revealed microscopic structure properties. Human blood-based analogs were found to be significantly stiffer and coagulated into solid clots in only 10 seconds with thrombin added but were found to lack real clot-like networking in their structure. Porcine whole blood-based analogs coagulated into solid clots faster with greater concentrations of CaCl2 added in the same 1:10 ratio to blood product volume and have yet to be characterized by DMA testing or histology. Conclusions: Solid clot analogs based on human and porcine blood products were successfully fabricated. Addition of thrombin improved analog stiffness and higher concentrations of CaCl2 led to faster coagulation of solid clots. Current analog results showed poor stiffness and microscopic structure. More work is needed to improve clot analog properties to better match those of real human thrombi and be suitable for thrombectomy device validation. Further trials and testing are also needed to determine the exact effects of coagulation temperature and motion conditions on clot analog properties.Deep Blue DOI
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thrombectomy clot analog thrombus
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